Helicobacter pylori is recognized as the most common bacterial infection associated with human chronic gastritis, peptic ulcer and gastric carcinoma. H. pylori infection has an estimated prevalence of about half the world's population, reaching up to 70% in developing countries and 20-30% in industrialized countries (Dunn et al., 1997). The vast majority of individuals acquire H. pylori in childhood; the prevalence of infection among children in developing countries is linked to a low socio-economic status and poor sanitation (Castillo-Rojas et al., 2004). H. pylori has been identified by the World Health Organization (WHO) as a class I carcinogen, as it increases the relative risk for gastric cancer at least six-fold. Gastric cancer is the second most common cause of mortality worldwide, and accounts for 700,000 annual deaths (Parkin et al., 2002).
Current eradication strategies of H. pylori are based on the use of proton pump inhibitors and antibiotics. However, the efficacy of chemotherapeutic intervention is limited by frequency of antibiotic resistance among H. pylori isolates and lack of immunity against re-infection. Thus, novel therapies are needed to provide a global strategy for the prevention and eradication of H. pylori infections.
While recent investigations have been focused on the role of protein components in the pathogenesis of H. pylori and their role in protective immunity (Ruggiero et al., 2003; Rossi et al., 2004), relatively few studies have explored the possibility of including antigens other than proteins in vaccine formulations (Angelakopoulos and Hohmann, 2000). For example, polysaccharide-based conjugate vaccines are known to prevent systemic infection and inhibit colonization of the host (Anderson et al., 1986; Chu et al., 1991; Pon et al., 1997; Passwell et al., 2001; Passwell et al., 2003). Recent studies of enteric pathogens have examined approaches based on LPS conjugates as candidate vaccines for human use (Gu et al., 1996; Mieszala et al., 2003; Cox et al., 2005; Yu and Gu, 2007).
Lipopolysaccharide (LPS) is a major cell surface component of H. pylori. Structural studies carried out on a number of H. pylori isolates (Monteiro, 2001) have resulted in a structural model of LPS consisting of an O-chain and a core oligosaccharide that is attached to a lipid A moiety. The structure of the O-chain polysaccharide backbone of most H. pylori strains is unique and displays type 2 and/or type 1 Lewis (Le) blood group determinants that mimic those present on the cell surface of human gastric and tumour cells (Wirth et al., 1996); these may be implicated in adverse autoimmune reactions leading to atrophic gastritis (Appelmelk et al., 1996). In addition, the outer core region of H. pylori LPS contains two unusual polymeric components: DD-heptoglycan and α1,6-glucan (Monteiro, 2001). The α1,6-glucan polymer in the outer core region H. pylori LPS isolates is synthesized by the product of the HP0159 open reading frame. The presence and expression of HP0159 gene in H. pylori is common.
A number of H. pylori LPS biosynthetic genes have been characterized and their role in pathogenesis and colonization determined (Logan et al., 2000; Logan et al., 2005; Hiratsuka et al., 2005; Chandan et al., 2007; Altman et al., 2008). H. pylori HP0826 mutants were constructed and it was demonstrated that this mutation resulted in formation of truncated LPS lacking Le antigen (Logan et al., 2000). However, full characterization of the structure of the LPS was not achieved.
Despite advances in the field, immunogenic epitopes effective across multiple types of H. pylori remain elusive.